96-well liquid solution micro-extraction and ultra-high-performance liquid chromatography tandem mass spectrometry analysis were used to evaluate a novel approach that combined micro-sampling of whole blood containing drugs of abuse. The most promising configuration was confirmed after being tested with various donor solutions, supported liquid membranes, and acceptor solutions. Opioids, cocaine, amphetamines, benzodiazepines, and z-hypnotics, among others, were included in the approach. 13 of the compounds had extraction recoveries greater than 70%, while the final four compounds had recoveries between 10 and 58%. The current method did not extract THC. Except for morphine, a linear calibration model was discovered for all drugs. For all compounds, except for morphine and zopiclone, which had a CV of 25% at LOQ, limits of quantitation were between 1 and 5 ng/mL, and inter-day precision and accuracy were within 20%. All framework impacts were inside 78-123%. Except for zolpidem and zopiclone, the samples remained stable for 14 days. The proposed method adheres to green chemistry principles due to its low cost, high sample throughput, semi-automated miniaturized sample preparation, use of dried blood micro samples, and Eco-Scale score of 78.
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